The challenges to develop and produce vaccines and therapeutics are immense, due to the ever-increasing or rapidly evolving pathogens, resulting in greater demand than supply. Rapid development and large-scale production of vaccines is the need-of-the-hour in case of an unexpected global calamity of a pandemic of massive scale. Plants offer a safe alternative for low-cost as well as large-scale production system for the vaccines, especially in developing countries. The review describes the strategies, advantages, challenges and prospects in the production of plant-based vaccines. A vaccine provides immunity against a disease. Vaccines used for immunization against diseases can be categorised into live attenuated vaccines, inactivated vaccines,subunit, recombinant or conjugated vaccines, toxoid-based vaccines, viral vector-based vaccines and nucleic acids-based vaccines.Live attenuated vaccine uses weakened or attenuated form of a pathogen, that causes a disease. They provide strong long-term immune response as they are similar to natural infection.
Attenuated vaccine may have small amount of the live virus which may be risky for people with weak immune system. Also, they require cold storage facilities. Live attenuated vaccines are used against smallpox,chickenpox, Measles, Mumps and Rubella etc. .Inactivated vaccines use killed or inactive pathogen and require booster doses of vaccine for immunity . Flu, pertussis, polio, rabies vaccines etc. are inactivated vaccines.Subunit, recombinant, polysaccharide and conjugate vaccines use part of the pathogen such as protein, capsid , sugar moiety etc. Subunitvaccines comprise of purified antigen derived from the pathogen, while conjugate vaccines, consist of a polysaccharide component of the pathogen that is poorly immunogenic, so that it is chemically linked to a protein. Recombinant subunit vaccines are safer since they do not have a pathogen and can also be scaled up. Since subunit vaccines consist of small fractions of the pathogen, immunogenicityis greatly decreased with respect to those derived from whole cells,generating the need for co-administering adjuvants to attain immune-protection.
They can be used in patients with weak immune systems and require booster doses to maintain immunity. These vaccines are used against Hepatitis B,Whooping cough, Human Papilloma Virus etc.Diphtheria and tetanus vaccines are toxoid vaccines .Viral vector-based vaccines such as Adenovirus or measles virus vectors are highly versatile platforms for vaccine development. Viral vector-based vaccines can be used for different viruses, delivered without additional adjuvants and can be administered as intramuscular, intranasal, intradermal and oral vaccination.High yield production processes and means of up scaling have been established for these vaccines so that they can be used immediately in case of apandemic outbreak. But viral vectors are genetically modified organisms considered as potential risks to human health and environment and unsafe due to persistent replication of attenuated vaccines. Viral vectors can integrate into the host genome, or undergo recombination during production, leading to emergence of uncharacterised or novel pathogens.
These safety concerns might also delay clinical studies in case of a pandemic. Viral vector-based vaccines are highly complex and comparatively cost-intensive .Nucleic acid-based vaccines employ antigen-encoding plasmid DNA or RNA or messenger RNA or viral replicons. Due to the ease of antigen manipulation they are also versatile. Vaccine can be developed against various pathogens such as virus, bacteria or parasite and administered as intramuscular or intradermal injections. A eukaryotic expression cassette carrying the antigen is inserted into a bacterial plasmid for propagation in E. coli . Minimal DNA constructs devoid of a bacterial backbone, such as the semi-synthetic minicircle DNA and the fully synthetic Doggy boneTM, have been developed to avoid safety issues related with selectable marker. DNA vector vaccine provides relatively low immune-genicity, since DNA vaccines must cross both plasma and nuclear membranes for protein expression, unlike the RNA vaccines which upon crossing plasmamembrane are translated. Encapsulation of DNA vaccines in lipid nanoparticles,adsorption to polymers and use of molecular adjuvants like cytokines can enhance the uptake of DNA vaccines and enhance the immune response. DNA vaccines have long-term persistence, however, potential risk of genomic integration of exogenous DNA into the host genome or chromosomes may result inmutagenes is and oncogenesis or new diseases. Molecular adjuvants like cytokines may also have undesirable, side-effects such as inflammation or autoimmunity.DNA vector-based antigen expression is the first effective vaccine against Ebola virus, Zika virus etc. and used against human pathogens such as HIV, influenza virus, malaria, hepatitis B virus, respiratory syncytial and herpes simplex virus .